DOI: 10.1083/jcb.200604113. To stabilize neutrophil polarity, PIP3 and Cdc42 augment RhoA activity at the back as well as signals at the front

To stabilize neutrophil polarity, PIP3 and Cdc42 augment RhoA activity at the back as well as signals at the front

10.1083/jcb.200604113

Crossref journal-article

Rockefeller University Press

The Journal of Cell Biology (291)

Abstract

Chemoattractants like f-Met-Leu-Phe (fMLP) induce neutrophils to polarize by triggering divergent signals that promote the formation of protrusive filamentous actin (F-actin; frontness) and RhoA-dependent actomyosin contraction (backness). Frontness locally inhibits backness and vice versa. In neutrophil-like HL60 cells, blocking phosphatidylinositol-3,4,5-tris-phosphate (PIP3) accumulation with selective inhibitors of PIP3 synthesis completely prevents fMLP from activating a PIP3-dependent kinase and Cdc42 but not from stimulating F-actin accumulation. PIP3-deficient cells show reduced fMLP-dependent Rac activity and unstable pseudopods, which is consistent with the established role of PIP3 as a mediator of positive feedback pathways that augment Rac activation at the front. Surprisingly, such cells also show reduced RhoA activation and RhoA-dependent contraction at the trailing edge, leading to the formation of multiple lateral pseudopods. Cdc42 mediates PIP3's positive effect on RhoA activity. Thus, PIP3 and Cdc42 maintain stable polarity with a single front and a single back not only by strengthening pseudopods but also, at longer range, by promoting RhoA-dependent actomyosin contraction at the trailing edge.

Bibliography

Van Keymeulen, A., Wong, K., Knight, Z. A., Govaerts, C., Hahn, K. M., Shokat, K. M., & Bourne, H. R. (2006). To stabilize neutrophil polarity, PIP3 and Cdc42 augment RhoA activity at the back as well as signals at the front. The Journal of Cell Biology, 174(3), 437â445.

Authors 7

Alexandra Van Keymeulen (first)
Kit Wong (additional)
Zachary A. Knight (additional)
Cedric Govaerts (additional)
Klaus M. Hahn (additional)
Kevan M. Shokat (additional)
Henry R. Bourne (additional)

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Dates

Type	When
Created	19 years, 1 month ago (July 24, 2006, 8:25 p.m.)
Deposited	2 years, 1 month ago (July 29, 2023, 6:16 a.m.)
Indexed	3 months, 2 weeks ago (May 21, 2025, 7:23 p.m.)
Issued	19 years, 1 month ago (July 24, 2006)
Published	19 years, 1 month ago (July 24, 2006)
Published Online	19 years, 1 month ago (July 24, 2006)
Published Print	19 years, 1 month ago (July 31, 2006)

Funders 0

None

BibTeX

@article{Van_Keymeulen_2006, title={To stabilize neutrophil polarity, PIP3 and Cdc42 augment RhoA activity at the back as well as signals at the front}, volume={174}, ISSN={0021-9525}, url={http://dx.doi.org/10.1083/jcb.200604113}, DOI={10.1083/jcb.200604113}, number={3}, journal={The Journal of Cell Biology}, publisher={Rockefeller University Press}, author={Van Keymeulen, Alexandra and Wong, Kit and Knight, Zachary A. and Govaerts, Cedric and Hahn, Klaus M. and Shokat, Kevan M. and Bourne, Henry R.}, year={2006}, month=jul, pages={437–445} }

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  "issued": {
    "date-parts": [
      [
        2006,
        7,
        24
      ]
    ]
  },
  "references-count": 40,
  "journal-issue": {
    "issue": "3",
    "published-print": {
      "date-parts": [
        [
          2006,
          7,
          31
        ]
      ]
    }
  },
  "URL": "http://dx.doi.org/10.1083/jcb.200604113",
  "relation": {},
  "ISSN": [
    "1540-8140",
    "0021-9525"
  ],
  "subject": [],
  "published": {
    "date-parts": [
      [
        2006,
        7,
        24
      ]
    ]
  }
}